Years after mass spectrometry served as an extremely useful analytical technique in many different fields, ionization process still remains to be one of the most important techniques for meeting the increasingly demanding applications. Matrix-assisted laser desorption/ionization (MALDI, Rapid Commun. Mass Spectrom. 1988, 2, 151) and electrospray ionization (ESI, Science 1989, 246, 64) are the two techniques signifying the emergence of the mass spectrometry in wide spread biological applications. Both methods along with other mature ionization methods operated for solid or liquid require careful treatment of the sample before ionization.
Therefore, the ionization methods for rapid detection without sample pretreatment are very much desired especially in the fields of homeland security, food safety, and illicit drug detection. The invention of the desorption electrospray ionization (DESI, Science 2004, 306, 471)) started the new area of direct analysis and it greatly reduces the time needed for analyzing samples in condensed phase. Many direct analysis methods have appeared since then such as Direct Analysis in Real Time (DART, Anal. Chem. 2005, 77, 2297), atmosphere solid analysis probe (ASAP, Anal. Chem. 77, 7826), electrospray-assisted laser desorption ionization (ELDI, Rapid Commun. Mass Spectrom. 2005, 19, 3701), and desorption atmospheric pressure photoionization (DAPPI, Anal. Chem. 2007, 79, 7867). Although each method has its distinct ionization mechanism, almost all of them were operated within a two-step process. The first step involves desorbing samples from surface and forming gaseous molecules, and the second step involves ionizing the gaseous molecules and forming molecular/quasi-molecular ions.
New ionization methods have appeared with different combinations of desorption step and ionization step. Each combination features its own advantages and provides possibilities for enhanced performance in a specific area. For example, both ELDI and laser desorption photoionization (LDPI, Chinese Patent Application No. CN101520432) use laser as their desorption source, but using electrospray in the ionization step in ELDI would generate more polar species compared with those generated by a VUV lamp as ionization source in LDPI. This difference makes ELDI more adequate for analyzing biological samples whereas LDPI is more intended for being used in the field of small molecule analysis.
For almost all of direct analysis methods, both desorption and ionization process happen at the atmospheric pressure for the convenience of sample loading. The interface between the atmospheric pressure and the vacuum is responsible for the major loss of the sensitivity since the majority of ions generated cannot enter the small capillary which separates the two pressure regions. The space charge effect in the ion plume makes the spread of ions even larger, and thus ions are more difficult to be entrained into the gas flow entering the capillary. Additionally, a detrimental factor for introducing ions into the capillary is that the electric field at the opening of the capillary on the entrance side will inevitably defocus the ions towards the wall of the capillary and cause neutralization. Furthermore, for those ions lucky enough to enter the capillary, there is still large chance for them to lose their charges by colliding with the inner wall of the capillary.
Alternatively, if the ionization process is moved into a region after the capillary, the problem of ion loss at the interface can be alleviated. In such case, only desorbed neutral molecules will be transferred through the capillary and therefore no space charge, defocusing electric field and neutralization effects exist anymore. One of such work has been reported by Marksteiner et al. in J. Phys. Chem. A 2009, 113, 9952 involving laser desorption at atmospheric pressure and vacuum UV ionization in a TOF source in a high vacuum region. The problem of such method from the stand point of sensitivity is that only a small portion of the neutrals can reach the ionization region due to the large distance required between the interface and the ionization region to maintain a high vacuum in the TOF source. For the neutrals, no electric lens can be used to guide and focus them, and this is very harmful to sensitivity especially considering the large spread of the neutrals by the supersonic expansion right after the capillary. Although the purpose of the work by Marksteiner et al. described above is not intended for enhancing the sensitivity, it does enlighten a way of separating the two steps for direct analysis in two different pressure regions, respectively.
Similar approaches have been taken for GC coupled MS with vacuum UV as a post-ionization means. Zimmermann et al. has used an electron-beam-pumped excimer VUV lamp to photoionize effluents from a GC in the first differential pumping region of the mass spectrometer (Anal. Chem. 2006, 78, 6365-6375), which has provided lots of useful information for utilizing single photon ionization method in vacuum. Another example is as mentioned in US Patent Publication No. 2010/0032059 in which the GC effluents were photoionized at low pressure by a VUV lamp fulfilled with the inert gas.
For various ionization methods, their ionization efficiencies differ very much from different pressures. Moreover, considering the different application fields of ion sources from one to another, it is an ideal solution to operate two or more ionization methods simultaneously while testing a complex mixture. Therefore, the issue becomes very important to make certain a suitable low pressure region in which one or more ionization means can achieve high ionization efficiency.